Cytokine modulation of the innate immune response in feline immunodeficiency virus - Infected cats

Background. In vitro data suggest that innate immune function in human immunodeficiency virus type 1 infected patients is compromised; however, in vivo studies are lacking. Feline immunodeficiency virus (FIV) infection in cats provides an excellent model to explore innate immune function in vivo. The innate response against Listeria monocytogenes is well understood, making it a useful immune probe. Methods. Recombinant L. monocytogenes carrying eukaryotic expression plasmids for feline tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, interferon (IFN)-gamma, and IL-15 were created to determine whether specific cytokines would modulate innate immune function. L. monocytogenes was delivered subcutaneously, and local lymph nodes were evaluated for size, cell subpopulations, and L. monocytogenes burden. Two months later, memory responses were evaluated by IFN-gamma enzyme-linked immunospot assay. Results. FIV-positive cats had significantly less lymph-node enlargement and a greater L. monocytogenes burden than FIV-negative control cats. TNF-alpha improved listericidal activity in FIV-negative control cats but not in FIV-positive cats, whereas IL-10 modestly reduced function in FIV-negative control cats. IFN-gamma improved memory responses but not clearance of L. monocytogenes. IL-15 improved innate function in FIV-positive cats and increased the percentage of natural killer cells. Conclusions. Lentivirus infection impairs innate immune function in vivo, and IL-15 can significantly restore function. We hypothesize that altered dendritic-cell function and increased regulatory T cell activity may underlie the innate immune defect in HIV infection.